Separating agent for optical isomer

ABSTRACT

The present invention is to provide a method of producing a separating agent for an enantiomeric isomer having high optical resolution power together with sufficient solvent resistance. That is, a method of producing a separating agent for an enantiomeric isomer comprising the steps of allowing the porous carrier to carry the optically active polymer compound by bringing the porous carrier into contact with a dope of the optically active polymer compound; and exposing a product to radiation.

TECHNICAL FIELD TO WHICH THE INVENTION BELONGS

The present invention relates to a separating agent for an enantiomericisomer, a method of producing the same, and the like. The separatingagent for an enantiomeric isomer is used for high-performance liquidchromatography (HPLC).

PRIOR ART

Optically active polymer compounds, especially polysaccharides orderivatives thereof such as ester or carbamate derivatives of celluloseor amylose, have been hitherto known to show high optical resolutionpower. Further, separating agents for chromatography having theoptically active polymer compounds physically adsorbed or carried onsilica gel have been also known as excellent separating agents eachshowing optical resolution power in a wide range, a large theoreticalplate number, and high durability (Y. Okamoto, M. Kawashima, and K.Hatada, J. Am. Chem. Soc., 106, 5357, 1984).

However, the separating agents can be used only under restrictedseparation conditions, since the optically active polymer compounds arecarried by silica gel using physical adsorption and thus solventscapable of dissolving the optically active polymer compounds cannot beused as mobile phases and the like. Further, solvents capable ofdissolving samples are restricted. A sample having a low degree ofsolubility in the solvents that can be used as the mobile phases causesa serious problem particularly in chromatographic separation. Moreover,there is another problem in that only limited washing fluids can be usedin washing away contaminants strongly adsorbed on the separating agents.In consideration of those points, the separating agents further havinghigh solvent resistance have been strongly required.

In order to solve such problems, there has been proposed a method offixing an optically active polymer compound such as a polysaccharidederivative on a carrier. JP-A 4-202141 discloses a separating agent foran enantiomeric isomer prepared through direct copolymerization of apolysaccharide derivative having a vinyl group, which is introduced intoa hydroxyl group site of a polysaccharide via an ester bond or aurethane bond, with a porous carrier having a vinyl group introducedthereinto.

In addition, the inventors of the present invention have disclosed inJP-B 7-30122 a technique of securing stability of both a polysaccharidederivative and silica gel by chemically bonding the polysaccharidederivative to the silica gel via an isocyanate derivative. The inventorsof the present invention have further proposed in JP-A 11-171800 amethod of fixing a cellulose derivative carried on silica gel throughradical copolymerization of styrene and divinylbenzene as a netstructure thereon.

However, those methods have problems in that preparation of a specialisocyanate derivative is required and that the production processrequires many steps. Thus, those methods are not suitable for theproduction thereof at an industrial level.

Meanwhile, WO97/04011 discloses a polysaccharide derivative prepared byphotochemically crosslinking a polysaccharide derivative having nophotopolymerizable functional groups, and a method of producing thesame. However, the method of photochemically crosslinking thepolysaccharide derivative having no photopolymerizable functional groupsinvolves very difficult control of a crosslinking rate, and the methoddoes not allow the polysaccharide derivative to be produced with goodreproducibility. Further, the method has a problem of a great difficultyin mass production due to a low light transmittance thereof andtherefore is not suitable for production in an industrial scale.

Accordingly, a separating agent for an enantiomeric isomer which hashigh optical resolution power inherent in an optically active polymercompound together with high solvent resistance and which can be producedeasily has been strongly desired.

DISCLOSURE OF THE INVENTION

An object of the present invention is therefore to provide a separatingagent for an enantiomeric isomer having high optical resolution powerinherent in an optically active polymer compound together withsufficient solvent resistance, a method of producing the same, and amethod of separating an enantiomeric isomer using the separating agent.

The present invention provides a separating agent for an enantiomericisomer, including an optically active polymer compound carried on aporous carrier, in which the optically active polymer compound isinsolubilized through exposure to radiation.

Further, the present invention provides a method of producing theseparating agent for an enantiomeric isomer, including the steps of:allowing the porous carrier to carry the optically active polymercompound by bringing the porous carrier into contact with a dope of theoptically active polymer compound; and exposing a product to radiation.

The present invention is particularly suitably used for high-performanceliquid chromatography (HPLC).

DETAILED DESCRIPTION OF THE INVENTION

Hereinafter, a method of producing a separating agent for anenantiomeric isomer of the present invention and the separating agentfor an enantiomeric isomer of the present invention will be described.Normal treatment conducted by a person skilled in the art may be addedto the following respective production steps, and the respectiveproduction steps may be conducted as separate independent steps or as acontinuous process.

A first step involves allowing a porous carrier to carry the opticallyactive polymer compound by bringing the porous carrier into contact witha dope of the optically active polymer compound.

A contact method between the porous carrier and the dope of theoptically active polymer compound is not particularly limited. Examplesof the contact method that can be applied include: a method involvingapplying a dope of an optically active polymer compound on a porouscarrier using an appropriate instrument or device; and a methodinvolving placing a porous carrier in a vessel, adding a dope of anoptically active polymer compound therein, and stirring and mixing thewhole by mechanical means or manually. After the optically activepolymer compound is carried on the porous carrier, a solvent remainingon the porous carrier together with the optically active polymercompound is preferably removed through vaporization.

Through treatment of the first step, the optically active polymercompound is carried on a surface of the porous carrier including itspores. A carried state differs depending on a combination of the porouscarrier and the optically active polymer compound. Examples of the stateinclude: a state in which an optically active polymer compound adheresonto a porous carrier through simple physical adsorption or the like;and a state in which a porous carrier and an optically active polymercompound are chemically bonded.

In the first step, a process including the steps of: dividing apredetermined amount of the dope of the optically active polymercompound into a plurality of parts; bringing part of the dope intocontact with the porous carrier; and drying a product may be repeated aplurality of times, as a step of allowing the porous carrier to carrythe optically active polymer compound.

The dope of the optically active polymer compound is divided intopreferably 2 to 20 parts, more preferably 2 to 10 parts.

The step of drying the product is for removing through vaporization asolvent used for obtaining the dope, and is conducted at normal pressureor reduced pressure, at normal temperatures or under heating, and in astream of a gas.

The steps of bringing part of the dope into contact with the porouscarrier and drying the product are repeated preferably 2 to 20 times,more preferably 2 to 10 times. An amount of the dope used each time maybe the same or different from those of other times.

The first step employs such a carrying method divided into a pluralityof times, and thus the optically active polymer compound can be carriedmore uniformly on the entire surface of the porous carrier. This ispreferable because higher separative power can be provided for theseparating agent for an enantiomeric isomer.

A porous organic carrier or a porous inorganic carrier can be used asthe porous carrier. Of those, a porous inorganic carrier is preferable.

Examples of appropriate porous organic carriers include polymersubstances made of polystyrene, polyacrylamide, polyacrylate, and thelike. Examples of appropriate porous inorganic carriers include silica,alumina, magnesia, glass, kaolin, titanium oxide, silicate, andhydroxyapatite. However, silica gel is particularly preferable. Whensilica gel is used, its surface is desirably subjected to silanetreatment (silane treatment using aminopropylsilane), plasma treatment,or the like in order to eliminate the influence of silanol remaining onthe silica gel surface and to enhance an affinity for the opticallyactive polymer compound. However, no problems occur even when thesurface is subjected to no treatment.

The porous carrier, particularly silica gel, has a particle sizepreferably in the range of 1 to 300 μm, more preferably in the range of2 to 100 μm, still more preferably in the range of 3 to 50 μm, and anaverage pore size preferably in the range of 60 to 8,000 Å, morepreferably in the range of 120 to 4,000 Å, still more preferably in therange of 300 to 3,000 Å. The particle size of the porous carrier issubstantially the particle size of a separating agent.

An average pore size of the porous carrier in the above range ispreferable because the solution of the optically active polymer compoundis sufficiently immersed in pores and the optically active polymercompound tends to evenly adhere to the inner walls of the pores.Furthermore, the pores are not closed, so the pressure loss of thefiller can be kept at a low level.

The optically active polymer compound is preferably an optically activepolymer compound containing no polymerizable unsaturated groups, is morepreferably a polysaccharide derivative. A polysaccharide derivativehaving all the same substituted derivatives is particularly preferablefrom the viewpoint of easily forming an orderly supermolecular structureof the optically active polymer compound.

A polysaccharide, from which the polysaccharide derivative is derived,may be a synthetic polysaccharide, a natural polysaccharide or a naturalproduct-modified polysaccharide. Anyone may be used as long as it isoptically active. One having a high regularity of form of bonding isdesirably used.

Examples of the polysaccharide include β-1,4-glucan (cellulose),α-1,4-glucan (amylose, amylopectin), α-1,6-glucan (dextran),β-1,6-glucan (pustulan), β-1,3-glucan (for example, curdlan,schizofillan, etc.), α-1,3-glucan, β-1,2-glucan (Crown Gallpolysaccharide), β-1,4-galactan, β-1,4-mannan, α-1,6-mannan,β-1,2-fructan (inulin), β-2,6-fructan (levan), β-1,4-xylan, β-1,3-xylan,β-1,4-chitosan, α-1,4-N-acetylchitosan (chitin), pullulan, agarose,alginicacid, etc. as well as amylose-containing starch.

Among these, cellulose, amylose, β-1,4-xylan, β-1,4-chitosan, chitin,β-1,4-mannan, inulin, curdlan, etc., from which high puritypolysaccharides are readily available, are preferred, with cellulose andamylose being particularly preferred.

The number average degree of polymerization (average number of pyranoseor furanose ring contained in one molecule) of these polysaccharides ispreferably 5 or more, more preferably 10 or more. There is no particularupper limit in the number average degree of polymerization but it isdesirably 1,000 or less in consideration of ease of handling. It is morepreferably 5 to 1,000, further more preferably 10 to 1,000, andparticularly preferably 10 to 500.

Each of polysaccharide derivatives obtained by bonding the part or wholeof the hydroxyl groups of the above polysaccharides with compoundshaving functional groups capable of reacting with hydroxyl groupsthrough ester bonds, urethane bonds, ether bonds, and the like can beused as the polysaccharide derivative.

Examples of a compound having a functional group capable of reactingwith a hydroxyl group, which may be any one as long as the compound hasa leaving group, include an isocyanic acide derivative, a carboxylicacid, an ester, an acid halide, an acid amide compound, a halogencompound, an aldehyde, and an alcohol. Aliphatic, alicyclic, aromatic,and heteroaromatic compounds of the above compounds can also be used.

As a particular preferable polysaccharide derivative, at least onederivative selected from the group consisting of a cellulose esterderivative, a cellulose carbamate derivative, an amylose esterderivative and an amylose carbamate derivative can be cited.

The solvent used for preparing the dope of the optically active polymercompound, indicating a solution or a dispersion liquid in the presentinvention, is not particularly limited as long as the solvent candissolve or disperse the optically active polymer compound, and thefollowing solvents can be used.

Examples of the solvent include: ketone-based solvents such as acetone,ethyl methyl ketone, and acetophenone; ester-based solvents such asethyl acetate, methyl acetate, propyl acetate, methyl propionate, methylbenzoate, and phenyl acetate; ether-based solvents such astetrahydrofuran, 1,4-dioxane, diethyl ether, and tert-butyl methylether; amide-based solvents such as N,N-dimethylformamide andN,N-dimethylacetamide; imide-based solvents such asN,N-dimethylimidazolidinone; halogen-based solvents such as chloroform,methylene chloride, carbon tetrachloride, and 1,2-dichloroethane;hydrocarbon-based solvents such as pentane, petroleum ether, hexane,heptane, octane, benzene, toluene, xylene, and mesitylene; urea-basedsolvents such as tetramethyl urea; alcohol-based solvents such asmethanol, ethanol, propanol, and butanol; acid-based solvents such asacetic acid, trifluoroacetic acid, formic acid, phenol, and catechol;and amine-based solvents such as diethylamine, triethylamine, andpyridine.

A mixing ratio between the optically active polymer compound and thesolvent is preferably 300 to 10,000 parts by mass, more preferably 300to 1,000 parts by mass of the solvent with respect to 100 parts by massof the optically active polymer compound.

A ratio of the dope of the optically active polymer compound to theporous carrier is preferably 50 to 5,000 parts by mass, more preferably100 to 1,000 parts by mass of the dope of the optically active polymercompound with respect to 100 parts by mass of the porous carrier.

A second step involves exposing the treated product obtained through thetreatment of the first step to radiation. A chemical bond is formedbetween the optically active polymer compounds in a crosslinkingreaction through the treatment of the second step. A chemical bond mayalso be formed between the porous carrier and the optically activepolymer compound by crosslinking.

Examples of the radiation include α-rays, β-rays, γ-rays, X-rays, and anelectron beam. Of those, γ-rays and an electron beam are particularlypreferably used, and γ-rays are most preferably used.

A γ-ray irradiation dose is preferably 1 kGy to 2,000 kGy, morepreferably 10 kGy to 1,000 kGy, furthermore preferably 50 kGy to 500kGy. For an exposure dose of 500 kGy or more, an electron beam ispreferably used.

When the treated product is exposed to radiation, a third component suchas diphenylmethane diisocyanate, epichlorohydrin, maleic chloride,isocyanate, epoxy, or dicarboxylic acid may be added for accelerating acrosslinking reaction by radiation. The third component is added in anamount of preferably 0.01 to 50 parts by mass, more preferably 0.05 to20 parts by mass, furthermore preferably 0.1 to 10 parts by mass withrespect to 100 parts by mass in total of the porous carrier and thepolymer compound.

In the treatment of the second step, the treated product obtained in thefirst step may be exposed to radiation in a state being dispersed in asolvent. It is preferable to expose the treated product to radiation ina state being dispersed in a solvent because the entire treated productcan be exposed to radiation uniformly. Such exposure is particularlysuitable for the treated product in a large amount as in production atan industrial level. An amount of the treated product that can beexposed to radiation at a time is preferably set in a range of about 1 gto about 100 kg, but may be set out of the above range.

When such treatment is conducted, a step of dispersing in a solvent aproduct having an optically active polymer compound carried on a porouscarrier is conducted after the treatment of the first step and beforethe treatment of the second step.

Examples of a dispersion solvent include water, an alcohol-basedsolvent, an ester-based solvent, and an ether-based solvent. Of those,water and an alcohol-based solvent are preferably used. Examples of thealcohol-based solvent particularly preferably used include methanol,ethanol, and 2-propanol.

A concentration of the dispersion liquid is preferably 30 to 80 mass %,particularly preferably 50 to 70 mass %. A concentration of thedispersion liquid of 30 mass % or more indicates an appropriate amountof a dispersant and provides high irradiation efficiency and anadvantageous irradiation cost. A concentration of the dispersion liquidof 80 mass % or less allows sufficient immersion of the optically activepolymer compound on the surface of the porous carrier in a solvent, tothereby favorably advance a crosslinking reaction through exposure toradiation.

After the second step, a step of washing the treated product obtainedthrough the treatment of the second step in an organic solvent capableof dissolving the optically active polymer compound can be provided. Thetreatment of the step allows removal of an optically active polymercompound forming no chemical bond through exposure to radiation in thesecond step.

The organic solvent to be used capable of dissolving the opticallyactive polymer compound can be the same as that of the first step.

A volume of the organic solvent used is preferably 5 to 15 times that ofthe treated product.

A washing method is not particularly limited, and examples thereof thatcan be used include: a method involving pouring an organic solvent onthe treated product and naturally filtering or filtering under reducedpressure at the same time; a method involving stirring the treatedproduct in an organic solvent under heating; and a method involvingpacking the treated product in a column tube once and then passing anorganic solvent therethrough with a pump. Such a washing step can berepeated a plurality of times as required.

Washing treatment conducted is such that an elution amount of theoptically active polymer compound is 1,000 ppm or less, preferably 700ppm or less, more preferably 500 ppm with respect to that of theseparating agent after the washing treatment when 1,000 ml of a solventcapable of dissolving the optically active polymer compound is passedthrough. An elution amount of the optically active polymer compound of1,000 ppm or less is effective for preventing impurity contamination inseparation of an enantiomeric isomer using the obtained separating agentfor an enantiomeric isomer.

An amount (mass ratio of the optically active polymer compound in theseparating agent for an enantiomeric isomer) of the optically activepolymer compound carried on the separating agent for an enantiomericisomer of the present invention is preferably 3 to 40 mass %, morepreferably 5 to 35 mass %, and furthermore preferably 10 to 30 mass %.

The separating agent for an enantiomeric isomer of the present inventionis used by packing in a column. The separating agent for an enantiomericisomer of the present invention may be packed into one column or aplurality of columns, and then may be applied to various types ofchromatography.

The separating agent for an enantiomeric isomer of the present inventionis useful as a separating agent for chromatography such as gaschromatography, liquid chromatography, supercritical chromatography,simulated moving bed chromatography, or thin-film chromatography. Theseparating agent for an enantiomeric isomer is particularly preferablyused as a separating agent for liquid chromatography.

The separating agent for an enantiomeric isomer of the present inventionhas high optical resolution power together with sufficient solventresistance, can be produced easily, and thus is useful for separation ofvarious enantiomeric isomers.

EXAMPLES

Hereinafter, the present invention will be described in detail byexamples, but the present invention is not limited thereto.

Example 1

(First Step)

Carrying of amylose tris[(S)-phenylethylcarbamate] on silica gel

1) Surface Treatment of Silica Gel

Porous silica gel (particle size of 20 μm) was reacted with3-aminopropyltriethoxysilane for aminopropylsilane treatment (APStreatment). The obtained APS treated-silica gel was reacted with anisocyanate compound, to thereby obtain silica gel subjected to carbamoylsurface treatment.

2) Synthesis of amylose tris[(S)-phenylethylcarbamate]

In a nitrogen atmosphere, 109 g (2 equivalents with respect to anamylose hydroxyl group) of (S)-phenylethylisocyanate was added to amixture containing 20 g of amylose and 500 ml of dry pyridine, and thewhole was stirred under heating at a reflux temperature of pyridine for24 hours. A reaction mixture was left standing to cool and then waspoured into methanol, to thereby precipitate the target amylosetris[(S)-phenylethylcarbamate] which was collected on a glass filter (atan yield of 93%).

3) Carrying of amylose tris[(S)-phenylethylcarbamate] on Silica Gel

20 g of amylose tris[(S)-phenylethylcarbamate] obtained in step 2) wasdissolved in tetrohydrofuran (THF), to thereby prepare a polymer dope.The polymer dope was divided into two parts, and half of the polymerdope was applied on 40 g of silica gel obtained in step 1) using amechanical stirrer. After the application, THF was distilled off underreduced pressure. The remaining half of the polymer dope was applieduniformly thereon in the same manner and THF was distilled off, tothereby obtain a product having the target amylosetris[(S)-phenylethylcarbamate] carried on silica gel.

(Second Step)

20 g of the treated product obtained in the first step was dried. 200 mlof methanol was added thereto, and the mixture was left standing for 1hour. Then, excess methanol was removed through filtration under reducedpressure. The treated product was put in a polyethylene reclosable bag,and the whole was irradiated with γ-rays of 300 kGy (irradiation devicewith an radiation source of cobalt 60 (radiation source loading of 37PBq)), to thereby obtain a separating agent for an enantiomeric isomer.

Example 2

A separating agent for an enantiomeric isomer was obtained in the samemanner as in Example 1 except that the dispersion solvent was changedfrom methanol to a mixed solvent of methanol/water=50/50 (volume ratio).

Example 3

A separating agent for an enantiomeric isomer was obtained in the samemanner as in Example 1 except that the dispersion solvent was changedfrom methanol to water.

Comparative Example 1

The treated product obtained after the treatment of the first step ofExample 1 (before the treatment of the second step) was used as aseparating agent.

Application Example 1

The separating agent for an enantiomeric isomer prepared in each ofExamples 1 to 3 and Comparative Example 1 was packed into a stainlesscolumn having a length of 25 cm and an inner diameter of 1.0 cm througha slurry packing method, to thereby prepare a separation column for anenantiomeric isomer. The following four compounds (racemic modification1 to 4) were optically resolved using the obtained separation column foran enantiomeric isomer.

In the formulae, ph represents a phenyl group.

<Analysis Conditions>

-   Mobile phase: n-hexane/2-propanol=9/1-   Column temperature: 25° C.-   Flow rate: 1.0 ml/min-   UV detector: 254 nm

A separation factor a in a liquid chromatography separation device isdefined as follows. Table 1 shows the separation factors a obtainedunder the above conditions.α=k2′/k1′

Here, k1′=(t₁−t₀)/t₀, and k2′=(t₂−t₀)/t₀. t₁ and t₂ each represent anelution time of an enantiomeric isomer, and to represents an elutiontime of tri-tert-butylbenzene. TABLE 1 Ex. 1 Ex. 2 Ex. 3 Com. Ex. 1 αRacemic modification 1 1.34 1.35 1.34 1.47 Racemic modification 2 2.32.31 2.34 2.47 Racemic modification 3 2.41 2.44 2.4 2.26 Racemicmodification 4 2.12 2.12 2.09 2.88

Example 4

6.5 g of the separating agent for an enantiomeric isomer obtained inExample 3 was placed on a glass filter, and 50 ml of THF was addedthereto. The mixture was stirred for a few minutes, and was filteredunder reduced pressure (a suction pressure of 4 kPa (=30 Torr) and apressure difference of 97 kPa (=730 Torr)) The procedure was repeated 3times. A separation factor a was determined using the obtained filler inthe same manner as in Application Example 1. Table 2 shows the results.

Comparative Example 2

A filler was washed in the same manner as in Example 4 except that theseparating agent for an enantiomeric isomer of Comparative Example 1 wasused. A separation factor a was determined using the obtained filler.Table 2 shows the results. TABLE 2 Racemic modification Ex. 4 Com. Ex. 21 1.0 1.0 2 1.58 1.0 3 2.05 1.0 4 1.68 1.0

Example 5

(First Step)

Carrying of amylose tris(3,5-dimethylphenylcarbamate) on silica gel

1) Surface Treatment of Silica Gel

Silica gel was subjected to surface treatment in the same manner as instep 1) of Synthesis Example 1.

2) Synthesis of amylose tris(3,5-dimethylphenylcarbamate)

In a nitrogen atmosphere, 10.0 g of amylose and 82.2 g (3 equivalents)of 3,5-dimethylphenylisocyanate were stirred in 360 ml of dry pyridineunder heating at a reflux temperature of pyridine for 60 hours, and thewhole was then poured into 6.0 L of methanol. A precipitated solid wascollected on a glass filter, washed with methanol a plurality of times,and subjected to vacuum drying (80° C., 5 hours). As a result, 35.3 g(yield of 95%) of a slightly yellowish white solid was obtained.

3) Carrying of amylose tris (3,5-dimethylphenylcarbamate) on Silica Gel

10 g of amylose tris(3,5-dimethylphenylcarbamate) obtained in step 2)was dissolved in ethyl acetate, to thereby prepare a polymer dope. Thetotal amount of the polymer dope was applied on 40.0 g of silica gelobtained in step 1) using a mechanical stirrer. After the application,the solvent was distilled off under reduced pressure, to thereby obtaina product having the target amylose tris(3,5-dimethylphenylcarbamate)carried on silica gel.

(Second Step)

The treated product obtained in the first step was dried and directlyirradiated with γ-rays, to thereby obtain a separating agent for anenantiomeric isomer irradiated with γ-rays. The conditions of the γ-rayirradiation were the same as those of Example 1.

Example 6

A separation factor a was determined in the same manner as inApplication Example 1 except that the separating agent for anenantiomeric isomer prepared in Example 5 was used. Table 3 shows theresults.

Comparative Example 3

A treated product after the treatment of the first step of Example 5(before the treatment of the second step) was used as a separatingagent, and a separation factor α was determined in the same manner as inApplication Example 1. Table 3 shows the results. TABLE 3 Racemicmodification Ex. 6 Com. Ex. 3 1 3.24 3.11 2 1.24 1.28 3 1.71 1.79 4 1.31.31

Example 7

6.5 g of the separating agent for an enantiomeric isomer obtained inExample 5 was placed on a glass filter, and 50 ml of THF was addedthereto. The mixture was stirred for a few minutes, and was filteredunder reduced pressure (a suction pressure of 4 kPa (=30 Torr) and apressure difference of 97 kPa (=730 Torr)) The procedure was repeated 3times. A separation factor α was determined using the obtained filler inthe same manner as in Application Example 1. Table 4 shows the results.

Comparative Example 4

A filler was washed in the same manner as in Example 7 except that theseparating agent for an enantiomeric isomer of Comparative Example 3 wasused. A separation factor α was determined using the obtained filler.Table 4 shows the results. TABLE 4 Racemic modification Ex. 7 Com. Ex. 41 2.56 1.0 2 1.0 1.0 3 1.42 1.0 4 1.19 1.0

1. A separating agent for an enantiomeric isomer, comprising anoptically active polymer compound carried on a porous carrier, theoptically active polymer compound having been insolubilized throughexposure to radiation.
 2. The separating agent for an enantiomericisomer according to claim 1, wherein the radiation comprises γ-raysand/or an electron beam.
 3. The separating agent for an enantiomericisomer according to claim 1, wherein the optically active polymercompound contains no polymerizable unsaturated group.
 4. The separatingagent for an enantiomeric isomer according to claim 1, wherein theoptically active polymer comprises a polysaccharide derivative.
 5. Theseparating agent for an enantiomeric isomer according to claim 4,wherein the polysaccharide derivative comprises at least one derivativeselected from the group consisting of a cellulose ester derivative, acellulose carbamate derivative, an amylose ester derivative and anamylose carbamate derivative.
 6. A method of producing the separatingagent for an enantiomeric isomer according to claim 1, comprising thesteps of: allowing the porous carrier to carry the optically activepolymer compound by bringing the porous carrier into contact with a dopeof the optically active polymer compound; and exposing an obtainedproduct to radiation.
 7. A method of producing the separating agent foran enantiomeric isomer according to claim 1, comprising the steps of:allowing the porous carrier to carry the optically active polymercompound by repeating a plurality of times a step including dividing apredetermined amount of the dope of the optically active polymercompound into a plurality of parts; bringing part of the dope intocontact with the porous carrier; and drying a product; and exposing theproduct to radiation.
 8. The method of producing the separating agentfor an enantiomeric isomer according to claim 6, further comprising thestep of dispersing in a dispersion solvent the product having theoptically active polymer compound carried on the porous carrier, afterthe step of allowing the porous carrier to carry the optically activepolymer compound, and then the step of exposing the product toradiation.
 9. The method of producing the separating agent for anenantiomeric isomer according to claim 6, further comprising the step ofwashing the product with an organic solvent capable of dissolving theoptically active polymer compound, after the step of exposing theproduct to radiation.
 10. The method of producing the separating agentfor an enantiomeric isomer according to claim 8, wherein the dispersionsolvent comprises at least one solvent selected from the groupconsisting of water, an alcohol-based solvent, an ester-based solvent,and an ether-based solvent.
 11. The method of producing the separatingagent for an enantiomeric isomer according to claim 6, wherein aradiation dose is 1 to 2,000 kGy.
 12. A method of separating anenantiomeric isomer with the separating agent for an enantiomeric isomeraccording to claim
 1. 13. A separating agent for an enantiomeric isomerproduced through the method of producing the separating agent for anenantiomeric isomer according to claim 6.